The proposed work is directed toward providing morphological and correlated biochemical information on the alterations which occur in hepatocytes from streptozotocin-diabetic rats. Hepatocytes from diabetic animals exhibit an increase in amount of smooth endoplasmic reticulum and microsomal glucose-6-phosphatase (G-6-Pase) activity per mg. membrane protein. The nature of this response for each of the microsomal elements (rough and smooth endoplasmic reticulum) will be used to monitor for alterations in the microsomal components. G-6 Pase is a key rate controlling enzyme in gluconeogenesis; thus its microsomal location makes it a notable enzyme to investigate in this study of the morphology and biochemistry of the diabetic state. Insulin effects on the hepatocyte will be determined by administering sufficient insulin to correct the streptozotocin-mediated diabetes. The ultrastructural and biochemical response to this treatment will then be followed and compared with that of the untreated diabetic animal. In addition, the effects of insulin withdrawal from insulin treated diabetic animal will be similarly examined. This will provide information on the early events following diabetic onset. The hypothesis is presented that the diabetic state may reflect in part an effect on hepatocyte morphology and microsomal membrane composition.